This invention relates to chemical compounds which display inhibition of Acyl-Coenzyme A: Cholestero-Acyl Transferase (ACAT). Compounds of this type may reduce cholesterol absorption and have an effect on atherosclerosis.
Atherosclerosis is the most common form of arteriosclerosis and is characterized by the build-up of phospholipids and esterified cholesterol in large and medium arteries causing them to be inelastic and thus weakened. These inelastic and occluded arteries are the most common cause of ischemic heart disease.
ACAT is an important enzyme for the intracellular esterification of cholesterol. Studies of this enzyme in cultured cells (M. S. Brown, J. Biol. Chem. 255 9344 (1980) has shown that increases in ACAT activity represent increases in the presence of cholesterol laden lipoproteins. Regulation of ACAT may help prevent the absorption of cholesterol in the intestinal mucosa, and may assist in the reversal of already present atherosclerotic lesions.